A randomized study comparing methylprednisolone plus chlorambucil versus methylprednisolone plus cyclophosphamide in idiopathic membranous nephropathy.

Abstract

To assess whether chlorambucil or cyclophosphamide may have a better therapeutic index in patients with idiopathic membranous nephropathy, we compared two regimens based on a 6-mo treatment, alternating every other month methylprednisolone with chlorambucil or methylprednisolone with cyclophosphamide. Patients with biopsy-proven membranous nephropathy and with a nephrotic syndrome were randomized to be given methylprednisolone (1 g intravenously for 3 consecutive days followed by oral methylprednisolone, 0.4 mg/kg per d for 27 d) alternated every other month either with chlorambucil (0.2 mg/kg per d for 30 d) or cyclophosphamide (2.5 mg/kg per d for 30 d). The whole treatment lasted 6 mo; 3 mo with corticosteroids and 3 mo with one cytotoxic drug. Among 87 patients followed for at least 1 yr, 36 of 44 (82%; 95% confidence interval [CI], 67.3 to 91.8%) assigned to methylprednisolone and chlorambucil entered complete or partial remission of the nephrotic syndrome, versus 40 of 43 (93%; 95% CI, 80.9 to 98.5%) assigned to methylprednisolone and cyclophosphamide (P = 0.116). Of patients who attained remission of the nephrotic syndrome, 11 of 36 in the chlorambucil group (30.5%) and 10 of 40 in the cyclophosphamide group (25%) had a relapse of the nephrotic syndrome between 6 and 30 mo. The reciprocal of plasma creatinine improved in the cohort groups followed for 1 yr for both treatment groups (P < 0.01) and remained unchanged when compared with basal values in the cohort groups followed for 2 and 3 yr. Six patients in the chlorambucil group and two in the cyclophosphamide group did not complete the treatment because of side effects. Four patients in the chlorambucil group but none in the cyclophosphamide group suffered from herpes zoster. One patient per group developed cancer. It is concluded that in nephrotic patients with idiopathic membranous nephropathy both treatments may be effective in favoring remission and in preserving renal function for at least 3 yr.

Remissions in Patients with Idiopathic Membranous Nephropathy Treated with Rituximab in Senegal

“…A significant decrease of more than 50% in mean PU at M3 after Rituximab administration (P < 0.001) was noted as reported in the literature (6,9). This remission rate at M6 was low compared to other studies using Rituximab (1, 6, 7, 10), alkylating agents (11)(12)(13)(14), or anticalcineurin (15,16). With this result, the main question is whether Rituximab should be used as first-line therapy in the management of IMN in sub-Saharan Africa?…”

Clinical Phenotypes and Predictors of Remission in Primary Membranous Nephropathy

“…Patients included in the study were either IS-naïve or received either a cyclophosphamide-based, calcineurin inhibitor-based or a rituximab-based regimen. Patients with a cyclophosphamide-based regimen received the classical Ponticelli cyclic regimen, consisting of three consecutive cycles lasting 2 months each (for a total of 6 months), where steroids were alternated with cyclophosphamide every other month [26,27]. Patients in the calcineurin-inhibitors (CNI) group received cyclosporine at an oral dose of 3.5-5 mg per kilogram per day, adjusted in order to obtain a target trough blood level of 125-175 ng/mL [24].…”

How Times Have Changed! A Cornucopia of Antigens for Membranous Nephropathy

“…Treatment for six months alternating cyclophosphamide with high-dose corticosteroids is still recommended for MN patients that are at very high risk of progression. This 'gold standard' in the treatment of MN of cyclic treatment with alkylating agents (cyclophosphamide or chlorambucil) and methyprednisolone, is described in the Ponticelli and 'modified Ponticelli' protocols (207) and to date, is the most efficacious at inducing remission. While effective, these cytotoxic drugs have multiple off-target side effects.…”